Format

Send to

Choose Destination
See comment in PubMed Commons below
J Hepatol. 2005 Mar;42(3):378-85.

Oncosis represents the main type of cell death in mouse models of cholestasis.

Author information

1
Laboratory of Experimental Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University, Auenbruggerplatz 15, A-8036 Graz, Austria. peter.fickert@klinikum-graz.at

Abstract

BACKGROUND/AIMS:

Since the mechanisms leading to hepatocyte death in cholestasis are not well defined, we aimed to obtain closer insights into the related pathogenetic principles.

METHODS:

Cell death was assessed in common bile duct ligated (CBDL) and cholic acid (CA)-fed mice, and compared to Fas agonist Jo2-injected mice by studying H and E-stained tissue sections, DNA ladder analysis, caspase-3-like activity assay, immunohistochemistry, double immunofluorescence microscopy for activated caspase-3 and cytokeratin (CK) 18, the TUNEL method, and electron microscopy.

RESULTS:

Jo2-treated mice showed activation of caspase-3, breakdown of the CK intermediate filament network, and classical morphological features of apoptosis. In contrast, in CA-fed and CBDL mice, oncosis characterized by cell swelling and ruptured cell membranes was the predominant type of cell death, whereas in both experimental conditions significant activation of caspase-3 was absent and typical CK alterations were rare despite frequent positivity of the TUNEL assay.

CONCLUSIONS:

(i) Oncosis represents the main type of hepatocyte death in acute cholestasis in mice. (ii) The importance of apoptosis in cholestasis may be overestimated if non-specific detection systems (e.g. TUNEL assay) are used.

PMID:
15710221
DOI:
10.1016/j.jhep.2004.10.016
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center